GLYCYRRHIZA GLABRA (LIQUORICE): A COMPREHENSIVE REVIEW OF ITS PHYTOCHEMISTRY, TRADITIONAL USES AND PHARMACOLOGICAL ACTIVITIES

Glycyrrhiza glabra L., commonly known as liquorice or licorice, is an important medicinal plant belonging to the family Fabaceae and has been used traditionally for centuries in various systems of medicine. The therapeutic potential of liquorice is largely attributed to its diverse phytochemical constituents, particularly triterpenoid saponins, flavonoids, isoflavonoids, chalcones, phenolic compounds and polysaccharides. Glycyrrhizin, glycyrrhetinic acid, liquiritin, liquiritigenin, isoliquiritigenin, glabridin and glabrene are among the major bioactive constituents associated with its pharmacological effects. Increasing experimental evidence suggests that G. glabra possesses a broad spectrum of pharmacological activities, including anti-inflammatory, antioxidant, antiviral, antimicrobial, hepatoprotective, anticancer, cardiovascular, neuroprotective, gastroprotective, antidiabetic, antifibrotic and immunomodulatory activities. Several of these effects are associated with modulation of oxidative stress, inflammatory mediators, nuclear factor-kappa B (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), apoptotic signalling and other cellular pathways. Liquorice-derived compounds have also attracted attention as potential therapeutic leads for hepatic, respiratory, infectious, gastrointestinal and inflammatory disorders. However, the pharmacological evidence remains predominantly preclinical, and considerable variation exists with respect to plant part, extract composition, dose, standardization and experimental model. In addition, excessive or prolonged exposure to glycyrrhizin and glycyrrhetinic acid may produce mineralocorticoid-like adverse effects, including sodium retention, hypokalemia, hypertension and edema. This review summarizes the phytochemical composition, traditional medicinal applications and major pharmacological activities of G. glabra, with emphasis on the proposed mechanisms of action and its potential for future therapeutic development.

• Bisht D, Rashid M, Arya RKK, Kumar D, Chaudhary SK, Rana VS, Sethiya NK. Revisiting liquorice (Glycyrrhiza glabra L.) as anti-inflammatory, antivirals and immunomodulators: potential pharmacological applications with mechanistic insight. Phytomedicine Plus., 2022; 2: 100206.
• Wahab S, Ahmad I, Irfan S, Siddiqua A, Usmani S, Ahmad MP. Pharmacological efficacy and safety of Glycyrrhiza glabra in treating respiratory tract infections. Mini-Reviews in Medicinal Chemistry, 2022; 22: 1476-1494.
• Wu Y, Wang Z, Du Q, Zhu Z, Chen T, Xue Y, et al. Pharmacological effects and underlying mechanisms of liquorice-derived flavonoids. Evidence-Based Complementary and Alternative Medicine, 2022; 2022: 9523071.
• Yang R, Yuan BC, Ma YS, Zhou S, Liu Y. The anti-inflammatory activity of liquorice, a widely used Chinese herb. Pharmaceutical Biology, 2017; 55:    5-18.
• Li X, Sun R, Liu R. Natural products in licorice for the therapy of liver diseases: progress and future opportunities. Pharmacological Research, 2019; 144: 210-226.
• Zhang Q, Ye M. Chemical analysis of the Chinese herbal medicine Gan-Cao (licorice). Journal of Chromatography A., 2009; 1216: 1954-1969.
• Nomura T, Fukai T, Akiyama T. Chemistry of phenolic compounds of licorice (Glycyrrhiza species) and their estrogenic and cytotoxic activities. Pure and Applied Chemistry, 2002; 74: 1199-1206.
• Zhang Z, Yang L, Hou J, Tian S, Liu Y. Molecular mechanisms underlying the anticancer activities of licorice flavonoids. Journal of Ethnopharmacology, 2021; 267: 113635.
• Wang ZY, Nixon DW. Licorice and cancer. Nutrition and Cancer, 2001; 39: 1-11.
• Zadeh JB, Kor ZM, Goftar MK. Licorice (Glycyrrhiza glabra Linn) as a valuable medicinal plant. International Journal of Advanced Biological and Biomedical Research, 2013; 1: 1281-1288.
• Yang R, Yuan BC, Ma YS, Zhou S, Liu Y. The anti-inflammatory activity of liquorice, a widely used Chinese herb. Pharmaceutical Biology, 2017; 55:   5-18.
• Zhang Q, Ye M. Chemical analysis of the Chinese herbal medicine Gan-Cao (licorice). Journal of Chromatography A., 2009; 1216(11): 1954-1969.
• Nomura T, Fukai T, Akiyama T. Chemistry of phenolic compounds of licorice (Glycyrrhiza species) and their estrogenic and cytotoxic activities. Pure and Applied Chemistry, 2002; 74(7):          1199-1206.
• Zhang Z, Yang L, Hou J, Tian S, Liu Y. Molecular mechanisms underlying the anticancer activities of licorice flavonoids. Journal of Ethnopharmacology, 2021; 267: 113635.
• Wang ZY, Nixon DW. Licorice and cancer. Nutrition and Cancer., 2001; 39(1): 1-11.
• Yao L, Sun T. Glycyrrhizin administration ameliorates Streptococcus aureus-induced acute lung injury. International Immunopharmacology, 2019; 70: 504-511.
• El-Magd NFA, El-Karef A, El-Shishtawy MM, Eissa LA. Hepatoprotective effects of glycyrrhizin and omega-3 fatty acids on nuclear factor-kappa B pathway in thioacetamide-induced fibrosis in rats. Egyptian Journal of Basic and Applied Sciences, 2015; 2: 65-74.
• Zadeh JB, Kor ZM, Goftar MK. Licorice (Glycyrrhiza glabra Linn) as a valuable medicinal plant. International Journal of Advanced Biological and Biomedical Research, 2013; 1: 1281-1288.
• Bahmani M, Saki K, Rafieian-Kopaei M, Karamati SA, Eftekhari Z, Jelodari M. The most common herbal medicines affecting Sarcomastigophora branches: a review study. Asian Pacific Journal of Tropical Medicine, 2014; 7: S14-S21.
• Bisht D, Rashid M, Arya RKK, Kumar D, Chaudhary SK, Rana VS, Sethiya NK. Revisiting liquorice (Glycyrrhiza glabra L.) as anti-inflammatory, antivirals and immunomodulators: potential pharmacological applications with mechanistic insight. Phytomedicine Plus., 2022; 2: 100206.
• Wahab S, Ahmad I, Irfan S, Siddiqua A, Usmani S, Ahmad MP. Pharmacological efficacy and safety of Glycyrrhiza glabra in treating respiratory tract infections. Mini-Reviews in Medicinal Chemistry, 2022; 22: 1476-1494.
• Wu Y, Wang Z, Du Q, Zhu Z, Chen T, Xue Y, et al. Pharmacological effects and underlying mechanisms of liquorice-derived flavonoids. Evidence-Based Complementary and Alternative Medicine, 2022; 2022: 9523071.
• Li X, Sun R, Liu R. Natural products in licorice for the therapy of liver diseases: progress and future opportunities. Pharmacological Research, 2019; 144: 210-226.
• Chen RY, Shi JJ, Liu YJ, Yu J, Li CY, Tao F, et al. The state-of-the-art antibacterial activities of glycyrrhizin: a comprehensive review. Microorganisms, 2024; 12(6): 1155. doi:10.3390/microorganisms12061155.
• Barai S, Tabassum T, Al Mamun A, Sagir S, Toha IW. An assessment of hepatoprotective activity of Glycyrrhiza glabra root extract against hepatic injured rodent model. Journal of Complementary and Alternative Medical Research, 2024; 25(10):   17-23. doi:10.9734/jocamr/2024/v25i10575.